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Comparative pharmacokinetics of 14C-sucrose in RG-2 rat gliomas after intravenous and convection-enhanced delivery.
Vavra, Michael; Ali, M Jaffer; Kang, Eric W-Y; Navalitloha, Yot; Ebert, Allison; Allen, Cathleen V; Groothuis, Dennis R.
Afiliação
  • Vavra M; Northwestern University Institute for Neuroscience, Northwestern University, Evanston, IL 60208, USA.
Neuro Oncol ; 6(2): 104-12, 2004 Apr.
Article em En | MEDLINE | ID: mdl-15134624
ABSTRACT
We compared tissue and plasma pharmacokinetics of 14C-sucrose in subcutaneous RG-2 rat gliomas after administration by 3 routes, intravenous bolus (i.v.-B; 50 microCi over 30 s), continuous i.v. infusion (i.v.-C, 50 microCi at a constant rate), and convection-enhanced delivery (CED, 5 microCi infused at a rate of 0.5 microl/min), and for 3 experimental durations, 0.5, 2, and 4 h. Plasma, tumor, and other tissue samples were obtained to measure tissue radioactivity. Plasma radioactivity in the CED group increased exponentially and lagged only slightly behind the IV-C group. After 90 min, plasma values were similar in all. Mean tumor radioactivity was 100 to 500 times higher in the CED group at each time point than in the i.v.-B and i.v.-C groups. Tumor radioactivity was homogeneous in the i.v. groups at 0.5 h and inhomogeneous at 1 and 2 h. In CED, radioactivity distribution was inhomogeneous at all 3 time points; highest concentrations were in tissue around tumor and in necrosis, while viable tumor contained the lowest and sometimes negligible amounts of isotope. Systemic tissue radioactivity values were similar in all groups. Efflux of 14C-sucrose from tumors was evaluated in intracerebral tumors (at 0.5, 1, 2, and 4 h) and subcutaneous tumors (at 0 to 0.5 h). Less than 5% of 14C activity remained in intracerebral tumors at each time point. The efflux half-time from the subcutaneous tumors was 7.3 +/- 0.7 min. These results indicate rapid efflux of drug from brain tumor and marked heterogeneity of drug distribution within tumor after CED administration, both of which may be potentially limiting factors in drug delivery by this method.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sacarose / Neoplasias Encefálicas / Sistemas de Liberação de Medicamentos / Glioma Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Neuro Oncol Ano de publicação: 2004 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sacarose / Neoplasias Encefálicas / Sistemas de Liberação de Medicamentos / Glioma Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Neuro Oncol Ano de publicação: 2004 Tipo de documento: Article